The ELISA assay has been automated and the apoA-I ELISA assay is presently being validated. Apolipoprotein E is a polymorphic protein with 3 common forms, apoE2, E3, and E4, with apoE2 bing catabolized the slowest and apoE4 the fastest in humans. ApoE2 has two reactive cysteines while apoE4 has these cysteines replaced with arginines. The slow metabolism of apoE2 was determined to be due predominantly to the altered conformation of the protein resulting from the substitution of cysteine for the arginine with only a small portion of the slower catabolism of the apoE2 being secondary to the slow catabolism of the disulfides dimers. ApoE is a glycoprotein that is present in plasma as di, mono, and asialo-apoE. When disialo-apoE was injected into subjects, there was little conversion to the mono or asialo forms indicating that either apoE is secreted with carbohydrate heterogeneity or that the apoE is modified following secretion but before it enters the plasma apoE pool. Tangier disease patients have low levels of HDL and apoA-I resulting from rapid catabolism of HDL. Two forms of apoA-I were isolated from Tangier subjects, one that co-migrated with normal apoA-I and one that was slightly shifted in molecular weight and isoelectric point. The normal form had a normal catabolic rate in kinetic studies while the shifted form was rapidly catabolized. This is consistent with the defect in Tangier disease being a post-translational modification of apoA-I in the circulation leading to rapid catabolism. Abetalipoproteinemia has been considered to be secondary to the absence of apoB synthesis. By utilizing sensitive immunological methods for the detection of apoB, it could be detected in plasma and in hepatocytes from abetalipoproteinemia subjects. This indicates that in at least some affected kindreds the defect is a post-translational abnormality that leads to the inability to secrete apoB.